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Time to onset of an adjudicated NMO/NMOSD attack [ Time Frame: From Day 1 of the study until on or before Day 197 of the randomized-controlled period. ]

time (days) to onset of an Adjudication Committee (AC) - determined NMO/NMOSD attack

Secondary Outcome Measures:

Attack Rate [ Time Frame: Annualized attack rate normalized by person/years during the open-label period, for a minimum of 1 year after the last subject enters and a maximum of 3 years after the last subject enters ]

Annualized attack rate (total number of adjudicated NMO/NMOSD attacks normalized by person-years) during the duration of the Open-label Period

Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: From the start of treatment with investigational product until the end of the Safety Follow-up Period, for a total of 12 months following the last dose of investigational product ]

Treatment-emergent adverse events, treatment-emergent serious adverse events (TESAEs), including laboratory measurements as well as their changes or shift from baseline over time

TMAX and CMAX [ Time Frame: From Day 1 of the study until on or before Day 197 of the randomized-controlled period. ]

mean MEDI-551 concentration versus time data will be plotted by AQP4-IgG seropositive and seronegative subjects

Incidence of Anti-Drug Antibodies (ADAs) Directed Against MEDI-551 [ Time Frame: From the start of treatment with investigational product until the end of the Safety Follow-up Period, for a total of 12 months following the last dose of investigational product ]

Incidence of anti-drug antibodies (ADAs) directed against MEDI-551 (both predose and postdose for each subject)

Worsening in EDSS [ Time Frame: From the start of treatment with invesigational product up to Day 197 of Randomised Control Period ]

Worsening from baseline in EDSS at last visit during the RCP

Change in Low-Contrast Visual Acuity Binocular Score [ Time Frame: From the start of treatment with invesigational product up to Day 197 of Randomised Control Period ]

MEDI-551 is a genetically engineered humanized monoclonal antibody that binds to the B cell specific surface antigen CD19 resulting in the depletion of B cells. CD19 positive (CD19+) B-lineage plasmablasts are responsible for the production of autoantibodies against the AQP4 channel protein.

The main objective of this study is to determine whether MEDI-551 compare to placebo decreases the risk of an attack in subjects with NMO/NMOSD.

This is a multicenter, multinational, randomized, double-masked, placebo controlled study with an open-label extension period to evaluate the efficacy and safety of intravenous (IV) MEDI-551 in adult subjects with NMO/NMOSD.

After a screening period, eligible subjects will enter a randomized-controlled period (RCP) of maximum 197 days where they will be randomized in a 3:1 ratio to receive either IV MEDI-551 or placebo. NMO/NMOSD attacks will be evaluated by the investigator and confirmed against the attack criteria by an independent Adjudication Committee (AC). Subjects for whom the attack was confirmed by the AC will be given the option to enroll into an open label period (OLP) with MEDI-551 treatment. Subjects who complete the RCP without experiencing an attack will be given the option to enroll into an OLP with MEDI-551 treatment. The OLP will continue for a minimum of 1 year and a maximum of 3 years after the last subject enter the OLP.

All subjects who discontinue from the RCP or the OLP will continue in a Safety Follow-up for a total of 12 months from last dose to evaluate the long-term safety of the investigational product.

Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:

18 Years and older (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Men and women 18 years or older with diagnosis of NMO/NMOSD

Confirmation of NMO/NMOSD status:

AQP4-IgG sero-positive NMO/NMOSD with at least one attack requiring rescue therapy in the last year or two attacks requiring rescue therapy in the last 2 years

AQP4-IgG sero-negative NMO with at least one attack requiring rescue therapy in the last year or two attacks requiring rescue therapy in the last 2 years

Able and willing to give written informed consent and comply with the requirements of the study protocol.

EDSS <= 7.5 (8 in special circumstances)

Men and women of reproductive potential must agree to use a highly effective method of birth control from screening to 6 months after final dose of the investigational product.

Exclusion Criteria:

Lactating and pregnant females

Treatment with any investigational agent within 4 weeks of screening

Known history of a severe allergy or reaction to any component of the investigational product formulation or history of anaphylaxis following any biologic therapy.

Known active severe bacterial, viral, or other infection or any major episode of infection requiring hospitalization.

History of alcohol, drug, or chemical abuse, or a recent history of such abuse < 1 year prior to randomization

Receipt of the following at any time prior to randomization:

Alemtuzumab

Total lymphoid irradiation

Bone marrow transplant

T-cell vaccination therapy

Receipt of rituximab or any experimental B-cell depleting agent within 6 months prior screening and B-cells below the lower limit of normal.

Receipt of IVIG within 1 month prior to randomization.

Receipt of any of the following within 3 months prior to randomization:

Natalizumab (Tysabri®)b.

Cyclosporin

Methotrexate

Mitoxantrone

Cyclophosphamide

Tocilizumab

Eculizumab

History of Hepatitis B and/or Hepatitis C (Hep B/C at screening)

Known history of a primary immunodeficiency (congenital or acquired) or an underlying condition such as human immunodeficiency virus (HIV) infection

History of malignancies, apart from squamous cell or basal cell carcinoma of the skin treated with documented success of curative therapy > 3 months prior to randomization

Any concomitant disease other than NMO/NMOSD that required treatment with oral or intravenous steroids at doses over 20 mg a day for over 21 days

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02200770